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Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR

Research Project

Project/Area Number 16K19461
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Respiratory organ internal medicine
Research InstitutionSapporo Medical University

Principal Investigator

Hasegawa Yoshihiro  札幌医科大学, 医学部, 助教 (90643180)

Co-Investigator(Renkei-kenkyūsha) TAKAHASHI MOTOKO  札幌医科大学, 医学部, 教授 (00303941)
TAKAHASHI HIROKI  札幌医科大学, 医学部, 教授 (60231396)
SAKUMA YUJI  札幌医科大学, 医学部, 准教授 (10364514)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肺サーファクタント蛋白質D / 変異型EGFR / 肺がん / 糖鎖 / レクチン / 肺サーファクタントタンパク質 / EGFR遺伝子変異 / 肺サーファクタント蛋白質 / EGFR / 肺サーファクタント / 肺コレクチン / SP-D
Outline of Final Research Achievements

We have previously demonstrated that SP-D suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. Analysis of patients with lung adenocarcinoma to examine associations between serum SP-D levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, high serum SP-D levels correlated with prolonged overall survival. We herein demonstrate that SP-D downregulates ligand-independent signaling in cells harboring EGFR mutations. SP-D inhibits ligand-independent dimerization of EGFR mutants and dimerization-independent activation of EGFR mutants. SP-D augmented the viability-suppressing effects of EGFR-TKIs. It is possible that the suppressive effects of SP-D on EGF signaling might be implicated in improved clinical outcomes in patients with EGFR mutant lung cancer and high serum SP-D levels.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2017 2016

All Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (4 results)

  • [Journal Article] Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients2017

    • Author(s)
      Umeda Y、Hasegawa Y、Otsuka M、Ariki S、Takamiya R、Saito A、Uehara Y、Saijo H、Kuronuma K、Chiba H、Ohnishi H、Sakuma Y、Takahashi H、Kuroki Y、Takahashi M
    • Journal Title

      Oncogene

      Volume: 36 Issue: 46 Pages: 6432-6445

    • DOI

      10.1038/onc.2017.253

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Surfactant protein A down-regulates epidermal growth factor receptor by mechanisms different from those of surfactant protein D2017

    • Author(s)
      Yoshihiro Hasegawa, Motoko Takahashi, Shigeru Ariki, Atsushi Saito, Yasuaki Uehara, Rina Takamiya, Koji Kuronuma, Hirofumi Chiba, Yuji Sakuma, Hiroki Takahashi, Yoshio Kuroki
    • Journal Title

      J Bill Chem

      Volume: 292 Issue: 45 Pages: 18565-18576

    • DOI

      10.1074/jbc.m117.800771

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Serum surfactant protein D predicts the outcome of patients with idiopathic pulmonary fibrosis treated with pirfenidone2017

    • Author(s)
      Ikeda Kimiyuki、Shiratori Masanori、Chiba Hirofumi、Nishikiori Hirotaka、Yokoo Keiki、Saito Atsushi、Hasegawa Yoshihiro、Kuronuma Koji、Otsuka Mitsuo、Yamada Gen、Takahashi Hiroki
    • Journal Title

      Respir Med.

      Volume: 131 Pages: 184-191

    • DOI

      10.1016/j.rmed.2017.08.021

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of the structural and functional features of surfactant protein A by acrolein in cigarette smoke2017

    • Author(s)
      Takamiya Rina、Uchida Koji、Shibata Takahiro、Maeno Toshitaka、Kato Masaki、Yamaguchi Yoshiki、Ariki Shigeru、Hasegawa Yoshihiro、Saito Atsushi、Miwa Soichi、Takahashi Hiroki、Akaike Takaaki、Kuroki Yoshio、Takahashi Motoko
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 8304-8304

    • DOI

      10.1038/s41598-017-08588-5

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Surfactant protein A inhibits growth and adherence of uropathogenic Escherichia coli to protect the bladder from infection.2017

    • Author(s)
      Hashimoto J., Takahashi M., Satio A., Murata M., Kurimura Y., Nishitani C., Takamiya R., Uehara Y., Hasegawa Y., Hiyama Y., Sawada N., Takahashi S., Masumori N., Kuroki Y., Ariki S.
    • Journal Title

      J. Immunol.

      Volume: 198 Issue: 7 Pages: 2898-2905

    • DOI

      10.4049/jimmunol.1502626

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Surfactant Protein A (SP-A) and SP-A-derived Peptide Attenuate Chemotaxis of Mast Cells Induced by Human β-defensin 3.2017

    • Author(s)
      Uehara Y., Takahashi M., Murata M., Saito A., Takamiya R., Hasegawa Y., Kuronuma K., Chiba H., Hashimoto J., Sawada N., Takahashi H., Kuroki Y., Ariki S.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 485 Issue: 1 Pages: 107-112

    • DOI

      10.1016/j.bbrc.2017.02.028

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] SP-Dによる変異型EGFR肺がんの制御機構2017

    • Author(s)
      長谷川喜弘, 梅田泰淳, 大塚満雄, 有木茂, 高宮里奈, 齋藤充史, 黒沼幸治, 千葉弘文, 高橋弘毅, 黒木由夫, 高橋素子
    • Journal Title

      分子呼吸器病

      Volume: 21 Pages: 80-83

    • Related Report
      2016 Research-status Report
  • [Journal Article] SP-DによるEGFR制御機構2017

    • Author(s)
      長谷川喜弘、高橋素子、高橋弘毅
    • Journal Title

      BIO Clinica

      Volume: 14 Pages: 130-134

    • Related Report
      2016 Research-status Report
  • [Journal Article] 肺サーファクタント蛋白質SP-Dの肺がんに対する新たな役割2016

    • Author(s)
      長谷川喜弘、高橋素子、高橋弘毅
    • Journal Title

      Medical Science Digest

      Volume: 42 Pages: 398-402

    • Related Report
      2016 Research-status Report
  • [Journal Article] N-glycans of growth factor receptors: their role in receptor function and disease implications.2016

    • Author(s)
      Takahashi M, Hasegawa Y, Gao C, Kuroki Y, Taniguchi N.
    • Journal Title

      Clinical Science

      Volume: 130 Issue: 20 Pages: 1781-1792

    • DOI

      10.1042/cs20160273

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] SP-A及びSP-A由来ペプチドはヒトβ-ディフェンシン3による肥満細胞の遊走を抑制する2016

    • Author(s)
      有木茂, 上原康昭, 村田雅樹, 高宮里奈, 長谷川喜弘, 齋藤充史, 千葉弘文, 黒沼幸治, 高橋素子, 高橋弘毅, 黒木由夫
    • Journal Title

      分子呼吸器病

      Volume: 20 Pages: 120-123

    • Related Report
      2016 Research-status Report
  • [Presentation] 肺サーファクタントタンパク質Dは変異型EGFRの活性化を阻害し、肺腺がんの進展を抑制する2017

    • Author(s)
      長谷川喜弘、梅田泰淳、大塚満雄、有木茂、高宮里奈、齋藤充史、高橋弘毅、 黒木由夫、高橋素子
    • Organizer
      第90回日本生化学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肺サーファクタント蛋白質Dによる変異型EGFRの制御機構2016

    • Author(s)
      長谷川喜弘, 佐久間裕司, 高橋素子
    • Organizer
      第75回日本癌学会学術総会, 2016年10月6日~8日
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Year and Date
      2016-10-06
    • Related Report
      2016 Research-status Report
  • [Presentation] SP-Dによる変異型EGFR肺がんの制御機構2016

    • Author(s)
      長谷川喜弘, 梅田泰淳, 高橋素子, 大塚満雄, 有木茂, 高宮里奈,齋藤充史, 高橋弘毅, 黒木由夫
    • Organizer
      第15回肺サーファクタント分子病態研究会
    • Place of Presentation
      札幌医科大学(札幌市)
    • Related Report
      2016 Research-status Report
  • [Presentation] 肺サーファクタント蛋白質DによるEGFR遺伝子変異陽性肺がんの制御機構2016

    • Author(s)
      長谷川喜弘, 高橋素子, 有木茂, 高宮里奈,齋藤充史, 高橋弘毅
    • Organizer
      第114回北海道癌談話会例会
    • Place of Presentation
      札幌医科大学(札幌市)
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2019-03-29  

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